Asymmetric catalysis of the Mukaiyama aldol addition reaction has been reported with complexes derived from Al, B, Sn(II), and Ti(IV) (Mikami et al., J. Am. Chem. Soc. 116:4077 (1994); Kobayashi et al., Tetrahedron 49:1761 (1993); Corey et al., Tetrahedron Lett. 33:6907 (1992); Parmee et al., Tetrahedron Lett. 33:6907 (1992); Kiyooka et al., Tetrahedron Lett. 33:4927 (1992); Furuta et al., J. Am .Chem. Soc. 113:1041 (1991); Furuta et al., Synlett (1991) 439; Parmee et al., J. Am. Chem. Soc. 113:9365 (1991); Kiyooka et al., J. Org. Chem. 56:2276 (1991); Kobayashi et al. Tetrahedron: Asymm. 2:635 (1991); and Reetz et al. Chem. and Ind. (London) 1986, 824). The levels of asymmetric induction for the addition of propionate, isobutyrate, and acetate derived silyl thioketene acetals to aldehydes parallel those obtained with chiral auxiliary-based methodologies (Evans, Aldrich Chemica Acta 15:23 (1982); Heathcock, in The Aldol Addition Reaction, Morrison, Ed. Asymmetric Synthesis; Academic Press, San Diego, CA 1984, Vol. 3, Chapter 2). However, silyl ketene acetals derived from O-alkyl acetates uniformly provide aldolates possessing lower levels of asymmetric induction.
The design of ligands for catalysts for the Mukaiyama aldol addition have primarily included bidentate chelates derived from optically active diols (Mikami et al., supra, Reetz et al., supra), diamines (Kobayashi et al., 1993, supra; Kobayashi et al., 1991, supra), amino acids (Corey et al., supra, Parmee et al., 1992, supra; Kiyooka et al., 1992, supra; Parmee et al., 1991 supra; Kiyooda et al., 1991, supra) and tartrates (Furuta et al., 1991, supra; Furuta et al., 1991, supra). Enantioselective reaction processes utilizing chiral Ti(IV) complexes have proven to be some of the most powerful transformations available to the synthetic chemist (Hanson et al., J. Am. Chem. Soc., 109:5765 (1987); Duthaler et al. Chem. Rev. 92:807 (1992)). However, the propensity of Ti(IV) complexes to form multinuclear aggregates results in complex dynamic equilibria that can render mechanistic and structural analysis difficult.
Therefore, it is an object of the present invention to provide catalysts for the enantioselective synthesis of .beta.-hydroxy carbonyl compounds.